This is a substantially revised version of a proposal based on " Synthetic Aspects of Kinetic Spiroketalization" that concerned the synthesis of cancer-active substances produced by blue-green algae of the family Oscillatoriaceae. The previous review recommended that we concentrate on methodological development. Accordingly, we have expanded our methodology and strategy in the area of oxygen heterocycle synthesis to include: 1) more useful substrates for dioxenium cation-olefin cyclizations; 2) a new synthesis of 4-oxo- tetrahydropyrans and spiroketals via condensation reactions of aldolate dianions and 3) a new convergent method for synthesizing highly oxygenated. The long term objectives of the research plan are the same as in the previous proposal: synthesis of medicinally important molecules containing multiply-oxygenated heterocycles as a critical subunit. Toward this objective, an important sub-goal is the further development and application of new methods of oxygen heterocycle synthesis. In particular, the developmental work has been targeted toward producing oxygen-functionalized tetrahydropyran and spiroketal subassemblies, key components of a variety of medicinally significant natural products. Preliminary studies have resulted in the production of various appropriately functionalized oxygen heterocycles as model substances relevant to eventual target molecule sytnhesis. The specific aims of the proposal are twofold: continued development of all three methods for the synthesis of functionalized oxygen heterocycles with regard to increasing both their utility and our understanding of the reactivity involved in each case; and synthesis of model substances related to the medicinally important compounds containing key oxygen heterocyclic arrangements, especially the cancer-active substances produced by the Oscillatoriaceae.